3-(2,6-dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one suppresses hydrogen peroxide-induced cytotoxicity on PC12 cells via activation of MAPK

TY - JOUR

T1 - 3-(2,6-dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one suppresses hydrogen peroxide-induced cytotoxicity on PC12 cells via activation of MAPK

AU - Nishina, Atsuyoshi

AU - Kimura, Hirokazu

AU - Kozawa, Kunihisa

AU - Sommen, Geoffroy

AU - Favero, Francesco

AU - Heimgartner, Heinz

AU - Koketsu, Mamoru

AU - Furukawa, Shoei

PY - 2011/12

Y1 - 2011/12

N2 - We newly synthesized organic selenium compounds (5-membered ring compounds) including 2-selenoxo-1,3-thiazolidin-4-ones (compounds A) and 3-alkoxy-4,5-dihydro-5-selenoxo-1H-1,2,4-triazole-1-carboxylates (compounds B). To address whether these compounds show antioxidative effects, we also examined their superoxide radical (O 2 -)-scavenging effects. Moreover, we examined the effects of compound Aa on the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinases (MAPK/ERK1/2) and suppression of hydrogen peroxide-induced cytotoxicity in rat pheochromocytoma cells (PC12 cells). We evaluated the O 2 --scavenging activities of the compounds by a chemiluminescence method, and activation of ERK1/2 in PC12 cells was evaluated by Western blot analysis. At 166 mmol/L, the O 2 --scavenging activities were markedly different among compounds A and B. 3-(2,6-Dimethylphenyl)-2- selenoxo-1,3-thiazolidin-4-one (compound Aa) exhibited the strongest superoxide anion-scavenging activity among compounds A and B. The concentration necessary for 50% inhibition of the activity (IC50) of compound Aa was 25.9 mmol/L. Compound Aa activated ERK1/2 of the PC12 cell, as did ebselen, and suppressed hydrogen peroxide-induced cytotoxicity more potently than ebselen. In addition, the toxicity of compound Aa was less than that of ebselen. From these results, it is assumed that compound Aa is a candidate drug to prevent oxidative stress-induced cell death.

AB - We newly synthesized organic selenium compounds (5-membered ring compounds) including 2-selenoxo-1,3-thiazolidin-4-ones (compounds A) and 3-alkoxy-4,5-dihydro-5-selenoxo-1H-1,2,4-triazole-1-carboxylates (compounds B). To address whether these compounds show antioxidative effects, we also examined their superoxide radical (O 2 -)-scavenging effects. Moreover, we examined the effects of compound Aa on the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinases (MAPK/ERK1/2) and suppression of hydrogen peroxide-induced cytotoxicity in rat pheochromocytoma cells (PC12 cells). We evaluated the O 2 --scavenging activities of the compounds by a chemiluminescence method, and activation of ERK1/2 in PC12 cells was evaluated by Western blot analysis. At 166 mmol/L, the O 2 --scavenging activities were markedly different among compounds A and B. 3-(2,6-Dimethylphenyl)-2- selenoxo-1,3-thiazolidin-4-one (compound Aa) exhibited the strongest superoxide anion-scavenging activity among compounds A and B. The concentration necessary for 50% inhibition of the activity (IC50) of compound Aa was 25.9 mmol/L. Compound Aa activated ERK1/2 of the PC12 cell, as did ebselen, and suppressed hydrogen peroxide-induced cytotoxicity more potently than ebselen. In addition, the toxicity of compound Aa was less than that of ebselen. From these results, it is assumed that compound Aa is a candidate drug to prevent oxidative stress-induced cell death.

KW - Animals

KW - Antioxidants/chemical synthesis

KW - Cell Proliferation/drug effects

KW - Cell Survival/drug effects

KW - Hydrogen Peroxide/toxicity

KW - Mitogen-Activated Protein Kinases/metabolism

KW - Organoselenium Compounds/chemical synthesis

KW - PC12 Cells

KW - Rats

KW - Superoxides/metabolism

U2 - 10.1177/1091581811419267

DO - 10.1177/1091581811419267

M3 - Journal article

C2 - 21960664

SN - 1091-5818

VL - 30

SP - 690

EP - 699

JO - International Journal of Toxicology

JF - International Journal of Toxicology

IS - 6

ER -